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The use of gamma functions in the calculation of organ perfusion functions for non-diffusible radioactive tracers.

This paper introduces a method for quantification of mean organ perfusion by the impulse response function using the experimental time-activity curves for the organ of interest and its supplying artery. These are approximated by gamma functions and a general expression for the impulse response function is then derived. In any particular case, the impulse response function can be calculated simply by insertion of the numerical parameters. The procedure combines speed with freedom from random measurement errors. As an example of a clinical application, the impulse response function of healthy brain tissue is calculated and some clinically important parameters are tabulated.

Blood Circulation

Experimental evolution of a new enzymatic function. II. Evolution of multiple functions for ebg enzyme in E. coli.

The evolution of ebgo enzyme of Escherichia coli, an enzyme which is unable to hydrolyze lactose, lactulose, lactobionate, or galactose-arabinoside effectively, has been directed in successive steps so that the evolved enzyme is able to hydrolyze these galactosides effectively. I show that in order for a strain of E. coli with a lacZ deletion to evolve the ability to use lactobionate as a carbon source, a series of mutations must occur in the ebg genes, and that these mutations must be selected in a particular order. The ordered series of mutations constitutes an obligatory evolutionary pathway for the acquisition of a new function for ebgo enzyme. A comparison of newly evolved strains with parental strains shows that when ebg enzyme acquires a new function, its old functions often suffer; but that in several cases old functions are either unaffected or are improved. I conclude that divergence of functions catalyzed by an enzyme need not require gene duplication.

Biological Evolution

Non invasive assessment of regional diastolic left ventricular function with first pass radionuclide functional imaging in ischaemic heart disease.

Functional images of regional distribution of rapid filling (RF) rates have been developed and applied at rest and on exercise for regional analysis of 301 coronary artery territories (103 compromised by coronary narrowings, 198 normal). The observed time-interval of RF averaged 209 ms at rest (range 200 to 280) and 172 ms on exercise (range 125 to 200 ms). Normal RF is directed to the apex, and it is deviated from territories with reduced compliance to normal territories. Sensitivity in detection and localization of territories compromised by coronary narrowings exceeds 90% at rest for the anterior and infero-posterior wall and is higher than that obtained from systolic functional images. Specificity amounts also to over 90% and is much higher than that observed with systolic functional images. During RF, moderate to severe loss in compliance results in initial regional paradoxical inward motion in 40 to 45% of anterior or postero-inferior segments eventually accompanied by significant inward displacement of blood. Thus, with functional imaging of regional RF rates one can establish dysfunction and functional significance of coronary narrowings.

Adult

Glycaemic thresholds for hypoglycaemic symptoms, impairment of cognitive function, and release of counterregulatory hormones in subjects with functional hypoglycaemia.

Nine patients with food-relieved hypoglycaemic symptoms, in whom insulinoma and other organic diseases presenting with hypoglycaemia had been ruled out, and nine matched controls, participated in the study. Subjects were studied during a 5-h controlled (Biostator) insulin-induced (1-2 mU kg-1 min-1) hypoglycaemic clamp. After 1 h of euglycaemia, we aimed to lower the glucose level in arterialized venous blood in a stepwise manner at 30-min intervals to 3.5, 3.0, and 2.0 mmol l-1, and to withhold these levels for a further 30 min. At euglycaemia and at the end of the latter steps, the visual reaction time and cognitive function (digit span, letter cancellation and trail making) were tested, together with recording symptoms and signs of hypoglycaemia. Counter-regulatory hormones were measured at 20-min intervals. In the patients, clinical signs and symptoms of hypoglycaemia developed at median blood glucose levels of 2.6-2.8 and 2.8-3.1 mmol l-1, respectively. By contrast, the blood glucose levels were 0.4-0.8 mmol l-1 lower in control subjects (P less than 0.05). Similarly, the median threshold for deterioration of visual reaction time was 2.8 mmol l-1 in patients and 2.1 mmol l-1 in controls (P less than 0.01). A similar trend was observed for the results of the neuropsychological tests. Visual reaction time deteriorated in all subjects, whereas the cognitive function of some of the subjects in each group remained unchanged during hypoglycaemia. The glycaemic thresholds for release of cortisol, glucagon and growth hormone were significantly higher in patients (P less than 0.05), whereas the thresholds for catecholamine release showed no significant difference from controls. Despite the comparable glucose infusion rates required to sustain each of the hypoglycaemic levels in the two groups, the control subjects achieved lower glucose levels, suggesting that there is resistance to insulin or glucose in functional hypoglycaemia. In conclusion, the present study suggests that the existence of a higher threshold for symptoms and signs, as well as for deterioration of brain function, may explain every-day hypoglycaemic symptoms, despite normal glucose levels, in subjects with functional hypoglycaemia. However, the hypothesis should be tested further using a blinded approach, including euglycaemic control studies.

Adult

Characterization of the point spread function and modulation transfer function of scattered radiation using a digital imaging system.

A digital radiographic system was used to measure the distribution of scattered x radiation from uniform slabs of Lucite at various thicknesses. Using collimation and air gap techniques, [primary + scatter] images and primary images were digitally acquired, and subtracted to obtain scatter images. The scatter distributions measured using small circular apertures were computer fit to an analytical function, representing the circular aperture function convolved with a modified Gaussian point spread function (PSF). On the basis of goodness of fit criterion, the proposed Gaussian function is a very good model for the scatter PSF. The measured scatter PSF's are reported for various Lucite thicknesses. Using the PSF's, the modulation transfer functions are calculated, and this spatial frequency information may have value in analytical scatter removal techniques, grid design, and air gap optimization.

Computers

Bacteriophage P22 virion protein which performs an essential early function. II. Characterization of the gene 16 function.

P16 is a virion protein and, as such, is incorporated into the phage head as a step in morphogenesis. The role of P16 in assembly is not essential since particles are formed without this protein which appear normal by electron microscopy. P16 is essential when the particle infects a cell in the following cycle of infection. In the absence of functional P16, the infection does not appear to proceed beyond release of phage DNA from the capsid. No known genes are expressed, no DNA is transcribed, and the host cell survives the infection, continuing to grow and divide normally. The P16 function is required only during infection for the expression of phage functions. Induction in the absence of P16 proceeds with the expression of early and late genes and results in particle formation. P16 must be incorporated during morphogenesis into progeny particles after both infection and induction for the progeny to be infectious. The P16 function is necessary for transduction as well as for infection. Its activity is independent of new protein synthesis and it is not under immunity control. P16 can act in trans, but appears to act preferentially on the phage or phage DNA with which it is packaged. The data from complementation studies are compatible with P16 release from the capsid with the phage DNA. In the absence of P16 the infection is blocked, but the phage genome is not degraded. The various roles which have been ruled out for P16 are: (i) an early regulatory function, (ii) an enzymatic activity necessary for phage production, (iii) protection of phage DNA from host degradation enzymes, (iv) any generalized alteration of the host cell, (v) binding parental DNA to the replication complex, and (vi) any direct involvement in the replication of P22 DNA. P16 can be responsible for: (i) complete release of the DNA and disengagement from the capsid, (ii) bringing the released DNA to some necessary cell site or compartment such as the cytoplasm, (iii) removal of other virion proteins from the injected DNA, and (iv) alterations of the structure of the injected DNA.

Adsorption

[Effects of Young's solution (YNG solution) on cardiac function and mitochondrial function during one hour ischemia at 30 degrees C and after reperfusion].

In a previous paper from this laboratory, protective effects of YNG solution on the myocardial mechanical function and metabolism of the heart arrested at 10 degrees C ascribable to the presence of Mg2+ were demonstrated. In order to further clarify the role played by Mg2+ in the protection, the present experiment was conducted using the isolated perfused guinea pig heart arrested at 30 degrees C. While the time to arrest of the contraction was equally short both with YNG (K+ + Mg2+) and K (K+) solutions, the time to resumption of contraction was significantly longer with K solution than with YNG solution, and the regular contraction was not resumed with the former solution. The recovery of the coronary flow, left ventricular pressure and dp/dt after reperfusion was around 100% with YNG solution, while the recovery was significantly poorer with K solution. Although the mitochondrial function was well maintained during the arrest both with YNG and K solution, the recovery of the mitochondrial function after reperfusion was observed only with YNG solution; severe damage was noted in mitochondria of the hearts arrested with K solution. There was a good correlation between the changes in mitochondrial function and those in cardiac function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Characterization of thyroglobulin in a patient with functioning and non-functioning benign thyroid tumors].

The chemical and immunological properties of thyroglobulin (Tg) in tissue obtained from a patient co-existed with two types of thyroid tumors, i.e., functioning and non-functioning, and were compared with the properties of Tg that was isolated from adjacent peripheral tissue. In the present observations, the Tg content was markedly increased in the non-functioning thyroid tumor. On the other hand, the Tg content in the functioning tumor was at the normal level. The iodine content of Tg was significantly lower in the non-functioning tumor than in peripheral tissues. Affinity with Lectins differed among Tg preparations, suggesting that the carbohydrate chain in the Tg was different in each nodule in a single individual.

Adenoma

[Erectile function and urinary function].

In recent years, with the great advance in neuro-urophysiological concept, the evaluation and limitations of clinical investigation for sexual (erection) function and bladder (urinary) function are continuously changing, so they should be correctly recognized at the time of actual interpretation. The common problems on these functional tests are standardization of terminology and of methodology, and difference of individual sensitivity. From a viewpoint of respective evaluation and limitations, AVSS, NPT, papaverine test, BCR for erectile function tests and CM, UFM, EMG, complex urodynamics for urinary function tests are reviewed.

Autonomic Nervous System Diseases

Functional assessment of elderly patients after percutaneous aortic balloon valvuloplasty: New York Heart Association classification versus functional status questionnaire.

Monitoring functional status in patients with cardiac disease has traditionally been done by using the New York Heart Association (NYHA) classification system. For various reasons, we found the NYHA system difficult to apply to elderly patients. We proposed that the functional status questionnaire (FSQ), which measures the ability to perform tasks, would more accurately assess the functional status of the elderly. In a study in 37 patients with a mean age of 76 years, who had aortic stenosis, we measured FSQ and NYHA scores at baseline, 1 month and 3 months. The difference in questionnaires was evident by the 3-month measurement. Individual patients were better evaluated by the FSQ. Six patients had an FSQ score of less than 72 (suggesting severe functional impairment) at 3 months but only two patients gave symptoms scored as NYHA class III or IV (cardiac disability). Five of six patients had a recurrent cardiac event subsequent to the 3-month follow-up. Changes in functional performance preceded symptomatic deterioration that was reflected only by the FSQ scores. The FSQ system more reliably predicted outcome than the NYHA system and appears to be a more useful tool in the evaluation of elderly patients with cardiac disease.

Activities of Daily Living

[Pathogenesis of functional retardation of physical and sexual development in adolescents. Status of somatotropic and gonadotropic function].

A study of somatotropic and gonadotropic functions in male adolescents with functional retardation of physical and sexual development has shown an important role of the deficiency of gonadotropins, especially FSH, in the pathogenesis of this condition. LH secretion in retarded physical development (RPD) is lowered to a lesser degree and positively correlates with testosterone deficiency. The feedback in the hypothalamohypophyseogonadal function in RPD is less frequently affected and to a lesser degree than gonadotropic functions. Of the tested methods (tests with TRH, L-DOPA and bromocriptine) STH reserves are better revealed with L-DOPA and TRH tests, gonadotropic reserves, especially LH,--with TRH and bromocriptine tests. The stimulating TRH effect on the growth hormone is indicative of the versatility and nonspecificity of its action on the pituitary gland in functional developmental disorders.

Adolescent

The graft-versus-host reaction and immune function. IV. B cell functional defect associated with a depletion of splenic colony-forming units in marrow of graft-versus-host-reactive mice.

Studies were conducted to determine whether a functional B cell defect occurred in the bone marrow of mice experiencing a GVH reaction (GVHBM). GVH reactions were induced in AxCBA F1 adult mice by an injection of A strain lymphoid cells. The GVH reaction was confirmed by immunosuppression and thymus histology. At various intervals after GVH induction, GVHBM was tested for its ability to restore B cell function in adult thymectomized irradiated mice reconstituted with normal thymocytes. GVHBM cells obtained seven days after GVH induction restored but slightly the plaque forming cell (PFC) response to sheep erythrocytes and the mitogen response to lipopolysaccharide (LPS). GVHBM cells obtained 10 days or later failed to reconstitute the PFC or LPS responses. GVHBM cells suppressed neither the T or B cell function of normal spleen cells nor the LPS mitogen response of normal bone marrow cells. In addition, the splenic colony-forming units (CFU-s) in GVHBM were slightly decreased by day 10 after GVH induction and markedly depressed by day 22 after GVH induction. These results suggest that the GVH reaction may affect two different events in B cell differentiation. The early decrease in functional B cells that occurs before there is any change in the CFU-s population suggests a direct effect on B cell production, whereas the later absence of functional B cells could be due to the marked decline in stem cell production (CFU-s).

Animals

Obesity and thyroid function. 3. Relationship between some indicators of thyroid function and the energy metabolism of striated muscle in obese women.

1. In a group of 23 obese women the relations between some indicators of thyroid function (thyroxine-binding globuline--T4BG, triiodothyronine-binding globuline--T3BG, Achilles tendon reflex--ART) on the one hand and activities of enzymes of the energy metabolism (hexokinase--HK, triose phosphate dehydrogenase--TPDH, lactate dehydrogenase--LDH, glycerol-3-phosphate dehydrogenase--GPDH, citrate synthease--CS, malate dehydrogenase--MDH, hydroxyacyl--COA dehydrogenase) in the quadriceps femoris muscle on the other hand were investigated. 2. Correlations were found between T4BG and TPDH, LDH and GPDH activities, between T3BG and TPDH and GPDH activities and between the value of the Achilles tendon reflex and TPDH activity. Functionally these enzymes activities are associated with glycolysis and hydrogen transport from cytoplasmatic NADH2. No correlations were found between enzymes of the aerobic metabolism incl. enzymes of fatty acid oxidation and indicators of thyroid function. 3. The results indicate a relationship between thyroid function and enzymes involved in glycolysis and hydrogen transport from cytoplasmatic NADH2. They do not suggest, however, the unequivocal conclusion that in obese women with reduced thyroid function there is a generally reduced energy supplying metabolism in skeletal muscle.

Achilles Tendon

Adherent cell function in murine T lymphocyte antigen recognition. II. Definition of genetically restricted and nonrestricted macrophage functions in T cell proliferation.

The mechanisms by which adherent cells, presumably of mononuclear phagocytic lineage, influence in vitro antigen-specific activation of murine T lymphocytes was examined. Two distinct functions for macrophages could be discerned. One macrophage function is dependent on a soluble factor produced by cultured adherent cells and is most easily studied with complex multideterminant antigens. This factor is neither antigen-specific nor MHC-restricted in its action in that PEC, regardless of haplotype, produce factor in the absence of antigen. A second function, antigen-specific T cell activation, is seen when antigens of more restricted heterogeneity are used, such as those under the control of Ir genes. This latter activity demands identity or partial identity between the antigen-presenting cell and the primed T cell, thus suggesting an additional specific, genetically restricted function for macrophages in in vitro antigen recognition. Whether these adherent cell functions are mediated by all or distinct subsets of cells was not established.

Animals

RETRACTED: Right ventricular function in patients with reduced left ventricular function undergoing myocardial revascularization.

Complex interrelationships exist between the right (RV) and the left ventricles (LV). Therefore, in 30 consecutive patients with reduced LV function (left ventricular ejection fraction [LVEF]) less than 40% undergoing myocardial revascularization, RV hemodynamics were studied from the beginning of anesthesia until the end of the operation. The data were compared with 30 consecutive patients with normal LVEF (greater than 70%). Ventricular function was assessed during left heart catheterization, which was carried out within 1 month of the operation. In addition to standard hemodynamic variables, RV ejection fraction (RVEF), RV end-diastolic volume (RVEDV), and RV end-systolic volume (RVESV) were monitored by the thermodilution technique. The two groups did not differ preoperatively with regard to RVEF, pressure (MAP, PAP, PCWP, RAP, RVPsyst, RVEDP), cardiac index (CI), and volume variables (RVESV, RVEDV). However, when the group with preoperatively reduced LVEF was subdivided into patients with severely reduced LVEF (less than 30%; n = 14; mean value 25.1%) and patients with moderately reduced LVEF (30%-40%; n = 16; mean value 37.3%), RVEF was significantly lower in the patients with a LVEF below 30% throughout the entire investigation period. RVEDV and RVESV were significantly higher in these patients. In conjunction with the lower RVEF and normal PAP, this suggests reduced RV function. It can be concluded that a severely reduced preoperative LVEF (less than 30%) may also be associated with impaired RV function.

Analysis of Variance

Primary biliary cirrhosis: relation between hepatic function and pulmonary function in patients who never smoked.

We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steady-state diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sjögren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans

[The effect of acute cellular rejection on liver function following orthoptic liver transplantation. Quantitative functional studies with the 14C-aminopyrine breath test].

To test the effect of acute cellular rejection on liver function as represented by cytochrome-P-450 enzyme activity, the 14C-aminopyrine breath test (ABT) was performed prospectively in 46 patients (31 men, 15 women; mean age 48 [15-66] years) who had undergone a total of 50 orthotopic liver transplantations. Routine biochemical tests were performed daily until the 30th postoperative day, while the ABT was done daily on days 1-10 and three times weekly on days 11-30, and liver puncture biopsies were obtained once weekly or more often if there was clinical suspicion of rejection. Histologically confirmed cellular rejection occurred within the stated period of observation in eight patients (five women, three men; median age 45 [18-59] years). Results of routine laboratory tests (transaminases, bilirubin, thromboplastin time), as well as bile-flow and body temperature, did not vary uniformly. On the other hand, results of ABT at the time of rejection showed a decrease in all patients by an average of 65% (P < 0.01). Changes in the ABT preceded those in other tests by 1-2 days in four patients, being the only measurable functional abnormality in one. All rejection episodes responded to glucocorticoid pulse-treatment (three times 1 g methyl-prednisolone). Using ABT results as criterion, liver function became normal after the glucocorticoid injection within 4-11 days. These data indicate that the ABT is suitable in the routine monitoring of transplant function, thus facilitating early diagnosis and controlled treatment of acute cellular rejection.

Acute Disease

Indoor air pollution and its effect on pulmonary function of adult non-smoking women: II. Associations between nitrogen dioxide and pulmonary function.

The association between nitrogen dioxide levels in homes and pulmonary function of 97 non-smoking adult women was investigated in a rural area in the Netherlands. The study population was a sub-sample of a longitudinal field study on chronic non-specific lung diseases which was started in 1965. Pulmonary function tests were performed at three-yearly intervals. NO2 was measured for one week in the winter in kitchen, living room and bedroom of each home. Cross-sectional analyses showed negative associations between NO2 exposure and several pulmonary function parameters as measured in the 1982 study. No significant association could be found between NO2 exposure and pulmonary function decline since the start of the study.

Adult